Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis

Medeiros, Gustavo C.; Gould, Todd D.; Prueitt, William L.; Nanavati, Julie; Grunebaum, Michael F.; Farber, Nuri B.; Singh, Balwinder; Selvaraj, Sudhakar; Machado‐Vieira, Rodrigo; Achtyes, Eric D.; Parikh, Sagar V.; Frye, Mark A.; Zarate, Carlos A.; Goes, Fernando S.

doi:10.1038/s41380-022-01652-1

Cited by 30 publications

(18 citation statements)

References 126 publications

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“…Neuroplasticity is considered as a key mechanism of ketamine antidepressive action. Meta-analysis on the potential biomarkers of ketamine efficacy indicated that patients who exhibited increased BDNF levels during treatment were more likely to become responders ( 89 ).…”

Section: Ketamine’s Mechanisms Of Antidepressant Actionmentioning

confidence: 99%

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

Więdłocha,

Marcinowicz,

Komarnicki

et al. 2024

Front. Psychiatry

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Borderline personality disorder (BPD) is diagnosed in 10-30% of patients with major depressive disorder (MDD), and the frequency of MDD among individuals with BPD reaches over 80%. The comorbidity of MDD and BPD is associated with more severe depressive symptoms and functional impairment, higher risk of treatment resistance and increased suicidality. The effectiveness of ketamine usage in treatment resistant depression (TRD) has been demonstrated in numerous studies. In most of these studies, individuals with BPD were not excluded, thus given the high co-occurrence of these disorders, it is possible that the beneficial effects of ketamine also extend to the subpopulation with comorbid TRD and BPD. However, no protocols were developed that would account for comorbidity. Moreover, psychotherapeutic interventions, which may be crucial for achieving a lasting therapeutic effect in TRD and BPD comorbidity, were not included. In the article, we discuss the results of a small number of existing studies and case reports on the use of ketamine in depressive disorders with comorbid BPD. We elucidate how, at the molecular and brain network levels, ketamine can impact the neurobiology and symptoms of BPD. Furthermore, we explore whether ketamine-induced neuroplasticity, augmented by psychotherapy, could be of use in alleviating core BPD-related symptoms such as emotional dysregulation, self-identity disturbances and self-harming behaviors. We also discuss the potential of ketamine-assisted psychotherapy (KAP) in BPD treatment. As there is no standard approach to the application of ketamine or KAP in individuals with comorbid TRD and BPD, we consider further research in the field as imperative. The priorities should include development of dedicated protocols, distinguishing subpopulations that may benefit most from such treatment and investigating factors that may influence its effectiveness and safety.

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Section: Ketamine’s Mechanisms Of Antidepressant Actionmentioning

confidence: 99%

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

Więdłocha,

Marcinowicz,

Komarnicki

et al. 2024

Front. Psychiatry

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“… 62 , 63 Recently, preclinical findings with classical serotonergic psychedelics (i.e., psilocybin, LSD, DMT, and DOI) indicate that neuroplasticity primarily involves TrkB and mTor receptors 191 , 192 , 193 and that TrkB‐signalling with psilocybin and LSD is independent of 5‐HT 2A activation. 191 Future research should exemplify whether 5‐MeO‐DMT is involved in TrkB‐signalling due to its promotion of brain‐derived neurotrophic factor and subsequent antidepressant effects following the atypical psychedelic ketamine 194 , 195 and conventional antidepressants. 196 , 197 Similarly, mTor‐signalling should be investigated due to its regulation of neuronal development and plasticity.…”

Section: Discussionmentioning

confidence: 99%

The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Tap

2024

Addiction Biology

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Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic‐assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4–12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short‐acting psychedelic 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5‐MeO‐DMT. Primarily, 5‐MeO‐DMT is able to induce mystical experiences and ego‐dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood‐related comorbidities consistent with the negative reinforcement and self‐medication paradigms. In addition, preliminary evidence indicates that 5‐MeO‐DMT modulates neural oscillations that might subserve ego‐dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5‐MeO‐DMT is characterized by neuroplasticity, anti‐inflammation, 5‐HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood‐related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action.

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“…Other relevant biomarkers have been thought to include, but are not limited to, alterations in pro-inflammatory cytokines interleukins (IL) 1, IL-6, IL-10, vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), as well as interferon-gamma (IFN-γ). Other receptors include the mu, kappa, and delta-opioid receptors, respectively [ 34 , 35 ]. The decrease in the expression of BDNF, a member of the neurotrophic protein family, is believed to display some type of causal relationship with neuropsychiatric disorders.…”

Section: Reviewmentioning

confidence: 99%

“…The decrease in the expression of BDNF, a member of the neurotrophic protein family, is believed to display some type of causal relationship with neuropsychiatric disorders. BDNF levels decrease in MDD and increase after antidepressant treatment, and similarly with ketamine and ESK [ 34 , 35 ].…”

Section: Reviewmentioning

confidence: 99%

Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review

Kumari,

Chaudhry,

Sagot

et al. 2024

Cureus

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The expansive spectrum of major depressive disorder (MDD) continues to pose challenges for psychiatrists to treat effectively. Oral antidepressant (OAD) medications that alter monoamine neurotransmitters, mainly selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), have been the mainstay of therapy for decades. Although these drugs have been largely beneficial, a considerable subset of patients do not respond adequately to multiple conventional therapies administered for an appropriate length of time, leading to a diagnosis of treatment-resistant depression (TRD). Ketamine, a non-monoaminergic drug, has long been known for its beneficial effects on TRD when given intravenously (IV). Between 2019 and 2020, an intranasal formulation of the S (+) enantiomer of racemic ketamine, esketamine (ESK), was granted “breakthrough designation" by the FDA and approved for the indications of TRD and MDD patients exhibiting acute suicidal intent. The objective of this narrative review was to review the academic literature and collect clinical evidence that may corroborate intranasal ESK's effectiveness for its approved indications while addressing its safety and tolerability profile, adverse effects, and impact on cognition. An overview of the drug's origins, pharmacology, and standard treatment regimen are provided. The outcomes from double-blinded randomized control trials (DB-RCTs) of ESK are outlined to demonstrate the efficacy and safety data leading to its FDA approval, along with its long-term post-market safety outcomes. Comparative trials between ESK and ketamine are then evaluated to highlight ESK's consideration as a more practical alternative to ketamine in common clinical practice. The authors further discuss currently approved and developing therapies for TRD, propose future research directions, and identify the inherent limitations of the review and further research. To conduct the research required, three digital databases (PubMed, Medline, and ClinicalTrials.gov ) were queried to search for key terms, including ketamine, esketamine, treatment-resistant depression, and biomarkers, using automation tools along with selective search engine results . After streamlining the results by title and abstract and removing duplicates, a total of 37 results were chosen, of which 18 are clinical trials. A reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score was the primary efficacy endpoint for most of these clinical trials. In conclusion, intranasal ESK, when used as an adjunct to market OADs, shows greater efficacy in treating TRD and MDD with suicidal intent compared to OADs and placebo alone and provides a more suitable alternative to IV ketamine. It is important to note that further research is required to fully understand the novel mechanism of action of ESK, as well as the establishment of a consensus definition of TRD, ...

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Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis

Cited by 30 publications

References 126 publications

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review

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